A novel gene, DBC2, was recently isolated and preliminary studies of DBC2 indicate that it is a potential candidate for a tumor suppressor. The long-term objectives include genetic analysis of DBC2 to validate it as a tumor suppressor; functional analysis of DBC2 to clarify physiological and pathological roles of DBC2; and studies of tumor physiology of DBC2 to provide new insights to breast and lung cancer development, The goal of this research project is to test the hypothesis that DBC2 is a tumor suppressor gene, Specific aims are: Specific Aim 1. We will utilize inducible gene expression systems to test the DBC2 function in vitro. Mutations will be introduced into predicted functional domains. Wild type and mutated DBC2 will be induced into various types of cells. Alterations of phenotypes and expression patterns will be analyzed. Specific Aim 2. Transcriptional regulation of DBC2 in cancer will be studied, Expression of DBC2 and the methylation status of the DBC2 promoter region will be investigated in cell lines and primary tumors. Specific Aim3. We will lay the foundations for studies on cellular functions of DBC2. Antibodies against DBC2 will be generated, Physiological expression of DBC2 in various tissues will be analyzed. Specific Aim 4. We will use embryonic stem (ES) cell technology to generate a Dbc2-deficient mouse model and analyze these mice for tumor susceptibility. [unreadable] [unreadable]